ArticleMolecular neurobiology2016
Rotenone Induces the Formation of 4-Hydroxynonenal Aggresomes. Role of ROS-Mediated Tubulin Hyperacetylation and Autophagic Flux Disruption.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- N-acetylcysteine: a potential therapeutic agent against toxicity of pesticides.Molecular biology reports · 2025Review
- Tubulin Acetylation and the Cellular Mechanosensing and Stress Response.Results and problems in cell differentiation · 2025Review
- Acetylation modification in the regulation of macroautophagy.Advanced biotechnology · 2024Review
- Antiproliferative Activities and SwissADME Predictions of Physicochemical Properties of Carbonyl Group-Modified Rotenone Analogues.ChemistryOpen · 2024Article
- Rotenone-Induced 4-HNE Aggresome Formation and Degradation in HL-1 Cardiomyocytes: Role of Autophagy Flux.International journal of molecular sciences · 2022Article
- Ghrelin alleviates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells.Neural regeneration research · 2022Article
- The role of altered protein acetylation in neurodegenerative disease.Frontiers in aging neuroscience · 2022Review
- Characterization of Signalling Pathways That Link Apoptosis and Autophagy to Cell Death Induced by Estrone Analogues Which Reversibly Depolymerize Microtubules.Molecules (Basel, Switzerland) · 2021Article
- Article
- Acetylation Modification During Autophagy and Vascular Aging.Frontiers in physiology · 2021Review
- Ischemic Postconditioning Alleviates Intestinal Ischemia-Reperfusion Injury by Enhancing Autophagy and Suppressing Oxidative Stress through the Akt/GSK-3Oxidative medicine and cellular longevity · 2020Article
- Fenpropathrin induces degeneration of dopaminergic neurons via disruption of the mitochondrial quality control system.Cell death discovery · 2020Article
- Interplay between reactive oxygen species and autophagy in the course of age-related macular degeneration.EXCLI journal · 2020Review
- Acylated Ghrelin is Protective Against 6-OHDA-induced Neurotoxicity by Regulating Autophagic Flux.Frontiers in pharmacology · 2020Article
- The true colors of autophagy in doxorubicin-induced cardiotoxicity.Oncology letters · 2019Review
- Autophagy induced by SAHA affects mutant P53 degradation and cancer cell survival.Bioscience reports · 2019Article
- AMPK-ERK/CARM1 Signaling Pathways Affect Autophagy of Hepatic Cells in Samples of Liver Cancer Patients.Frontiers in oncology · 2019Article
- Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines.Drug design, development and therapy · 2018Article
- Pigment Epithelium-derived Factor Protects Retinal Pigment Epithelial Cells Against Cytotoxicity "In Vitro".Advances in experimental medicine and biology · 2018Article
- Acetylome in Human Fibroblasts From Parkinson's Disease Patients.Frontiers in cellular neuroscience · 2018Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress causes cellular damage by (i) altering protein stability, (ii) impairing organelle function, or (iii) triggering the formation of 4-HNE protein aggregates. The catabolic process known as autophagy is an antioxidant cellular response aimed to counteract these stressful conditions. Therefore, autophagy might act as a cytoprotective response by removing impaired organelles and aggregated proteins. In the present study, we sought to understand the role of autophagy in the clearance of 4-HNE protein aggregates in ARPE-19 cells under rotenone exposure. Rotenone induced an overproduction of reactive oxygen species (ROS), which led to an accumulation of 4-HNE inclusions, and an increase in the number of autophagosomes. The latter resulted from a disturbed autophagic flux rather than an activation of the autophagic synthesis pathway. In compliance with this, rotenone treatment induced an increase in LC3-II while upstream autophagy markers such as Beclin- 1, Vsp34 or Atg5-Atg12, were decreased. Rotenone reduced the autophagosome-to-lysosome fusion step by increasing tubulin acetylation levels through a ROS-mediated pathway. Proof of this is the finding that the free radical scavenger, N-acetylcysteine, restored autophagy flux and reduced rotenone-induced tubulin hyperacetylation. Indeed, this dysfunctional autophagic response exacerbates cell death triggered by rotenone, since 3-methyladenine, an autophagy inhibitor, reduced cell mortality, while rapamycin, an inductor of autophagy, caused opposite effects. In summary, we shed new light on the mechanisms involved in the autophagic responses disrupted by oxidative stress, which take place in neurodegenerative diseases such as Huntington or Parkinson diseases, and age-related macular degeneration.
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